Diuretics
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Direct answer
Diuretics are classified by their site of action in the nephron: loop diuretics block the Na-K-2Cl cotransporter in the thick ascending limb, thiazides block the Na-Cl symporter in the distal convoluted tubule, potassium-sparing agents act in the late distal tubule and collecting duct, and acetazolamide inhibits carbonic anhydrase in the proximal tubule. NEET-PG tests the site of action together with the signature electrolyte profile of each class — above all the opposite handling of calcium by loops (lose calcium) and thiazides (retain calcium).
What you must remember
- Loop diuretics (furosemide, bumetanide, torsemide): most powerful natriuresis; cause hypokalaemia, metabolic alkalosis, hypomagnesaemia, hyperuricaemia, ototoxicity and hypocalcaemia through urinary calcium loss; first choice in pulmonary oedema, resistant oedema and renal impairment.
- Thiazides (hydrochlorothiazide, chlorthalidone, indapamide): cornerstone antihypertensives; cause hypercalcaemia, hypokalaemia, hyponatraemia, hyperuricaemia, hyperglycaemia and dyslipidaemia; used for calcium-oxalate stone prophylaxis in hypercalciuric patients; lose efficacy in advanced renal failure, metolazone being the exception.
- Aldosterone antagonist spironolactone: used in heart failure with reduced ejection fraction, ascites and Conn syndrome; causes hyperkalaemia and metabolic acidosis; endocrine effects include gynaecomastia and menstrual irregularity; eplerenone is the selective analogue with fewer antiandrogenic effects.
- ENaC blockers amiloride and triamterene: potassium-sparing, useful alongside thiazides to offset potassium loss; amiloride also reduces lithium-induced nephrogenic diabetes insipidus.
- Acetazolamide: carbonic anhydrase inhibitor producing bicarbonaturia, alkaline urine and hyperchloraemic metabolic acidosis; used in glaucoma and altitude sickness; avoid in cirrhosis and sulfa-allergic patients.
- Osmotic diuretic mannitol: increases tubular fluid osmolarity, used for cerebral oedema; contraindicated in anuria and pulmonary oedema.
- Aquaretics (tolvaptan): vasopressin V2 antagonists that promote free-water excretion in hyponatraemia.
Common confusion
Loop versus thiazide is the classic trap, and calcium settles it: loops abolish the lumen-positive potential in the thick ascending limb, so calcium is lost in urine and serum calcium falls, whereas thiazides enhance distal calcium reabsorption, so serum calcium rises — the reason thiazides prevent calcium stones while loops cannot. Potassium handling is the second differentiator: both classes waste potassium, so the exam point is which agent to add for a hypokalaemic patient — a potassium-sparing diuretic. Loops also retain efficacy in renal failure, where thiazides fail — metolazone excepted.
Exam-focused takeaway
NEET-PG questions on diuretics are site-of-action and electrolyte-matching stems: identify the cotransporter blocked, predict the potassium, calcium, urate and acid-base consequences, and choose the class for a named scenario — acute pulmonary oedema, hypertension, hypercalcaemia of malignancy (loop), recurrent calcium stones (thiazide), ascites or Conn syndrome (spironolactone), and glaucoma or altitude sickness (acetazolamide). Adverse-effect vignettes featuring ototoxicity, gynaecomastia or metabolic acidosis are common. Master each class as site, electrolyte fingerprint and best indication — that chain answers almost every question on this reliably repeated topic.
Frequently asked questions
Where do loop and thiazide diuretics act?
Loops block the Na-K-2Cl cotransporter in the thick ascending limb; thiazides block the Na-Cl symporter in the distal convoluted tubule.
Why do loops lower and thiazides raise serum calcium?
Loops abolish the lumen-positive transepithelial potential that drives paracellular calcium reabsorption, causing calciuria, while thiazides stimulate distal calcium reabsorption, retaining calcium.
Which diuretic is preferred in acute pulmonary oedema?
Intravenous furosemide, for its rapid venodilation and powerful natriuresis; loops also remain effective in renal impairment where thiazides fail.
What are the adverse effects of spironolactone?
Hyperkalaemia and metabolic acidosis, plus antiandrogenic effects such as gynaecomastia, breast tenderness and menstrual irregularity; eplerenone causes less gynaecomastia.
Why is acetazolamide used in glaucoma and altitude sickness?
By inhibiting carbonic anhydrase it reduces aqueous humour formation in the eye and produces a metabolic acidosis that stimulates ventilation at altitude, alongside its bicarbonaturia.
Which diuretic is safe to combine with a loop in resistant oedema?
Metolazone, a thiazide-like agent that retains efficacy in renal impairment, is classically added to a loop for sequential nephron blockade under close electrolyte monitoring.